March 20, 2013

Researchers Find New Genes To Detect And Prevent Breast Cancer

A new study from Northwestern Medicine has identified a set of genes that may predict which women are at high risk for getting breast cancer that is sensitive to estrogen. These women would be helped by taking drugs to prevent the cancer's development. The results of the study will be published in the journal Cancer Prevention Research.

"We now have the possibility of predicting if a preventive drug will work for a woman at high risk of breast cancer, so that we don't expose women to the risks and side effects of this drug if it won't help them," said Seema Khan, M.D. Khan who is currently the co-leader of the breast cancer program at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University, a doctor at Northwestern Medical Hospital, and the Blum Family Professor of Cancer Research at Northwestern University Feinberg School of Medicine.

Women who are at high risk for breast cancer based on having a close relative with breast cancer or certain types of benign changes identified in the breast during biopsy have the option of taking drugs such as tamoxifen and raloxifene to prevent breast cancer. However, the drugs are only effective against breast cancer that is sensitive to estrogen, known as hormone receptor-positive breast cancer. These drugs do not affect breast cancer that is not sensitive to estrogen or hormone receptor-negative breast cancer. At highest risk for this kind of breast cancer are young women and women of African American descent.

It has not been possible to predict which of these two types of breast cancer will occur in a high risk woman until now. The cancer prevention drugs have numerous side effects as well, and many women choose not to take them. Many of the newly discovered genes are involved in fat metabolism. The research team found the new genes present at a higher level in the healthy breast tissue of women with hormone receptor-negative breast cancer. This would potentially allow women to make an informed choice about the medications based on better information about the type of breast cancer for which they are at risk. The genes could also provide potential targets for the development of preventative therapy for hormone receptor-negative breast cancer.

"Identifying these genes also gives us a target for new therapies," Khan said. "Once we understand what regulates these genes, we can try to develop a therapy to switch them off."

"It was a surprise for us that these genes are related to fat metabolism, because we would have expected them to be related to estrogen," said Jun Wang, a research assistant professor of surgery at Feinberg and first author on the study. "Now we want to find out why women have higher levels of these genes."

By examining the gene expression in the other, healthy breasts of women who had a primary cancer, the team hoped to find a way to identify women at risk for estrogen-sensitive breast cancer. According to previous research, if women who have cancer in one breast develop it in the second breast, the second cancer is likely to have the same hormone receptor as the first.

The team analyzed the genes in the unaffected breasts of 30 women. Fifteen of the participants had estrogen-positive breast cancer and fifteen had estrogen receptor-negative breast cancer. Using a second group of women (12 positive and 12 negative) and a control group of 12 women who had no cancer, they validated the results. Of all women in the study, two-thirds were postmenopausal and one-third were premenopausal.

The study identified 13 genes with significantly higher expression levels in samples obtained from women with estrogen receptor-negative breast cancer. Eight of these genes were associated with lipid or fat metabolism, and several are known to be abnormally expressed in breast cancer cells, adding strength to the findings.